The present invention relates to methods of ring opening polymerization and catalysts therefor, and more specifically, to salt catalysts for ring opening polymerizations.
Ring-opening polymerization catalysts have allowed access to advanced materials in areas as diverse as adhesives and drug delivery. The first catalysts for ring opening polymerization were inorganic materials (e.g., aluminum, zinc, and tin compounds), which demonstrated excellent fidelity and control needed for construction of higher order polymer architectures. Unfortunately, the residual metal remaining in the resultant polymers proved problematic for microelectronic applications. Consequently, organic compounds were investigated to replace highly active metal-containing catalysts. In 2001, the first ring opening polymerization of lactide catalyzed by an organocatalyst, 4-dimethylaminopyridine (DMAP), was demonstrated, setting the stage for future discoveries of phosphines, carbenes, and amidine/guanidines for the polymerization of cyclic esters.
Transition metals are thought to catalyze the polymerization of cyclic esters (lactide, valerolactone, caprolactone, and the like) through a coordination-insertion mechanism. In comparison, organocatalyzed polymerizations were originally postulated to go through an activation mechanism in which DMAP or other electron donating organic catalyst, acting as a nucleophile (Nuc:) as shown in Scheme 1, form an activated complex with the monomer carbonyl, thereby lowering the activation energy for subsequent attack by the weaker nucleophilic hydroxyl group.
More recently this activation theory was amended in order to account for the theoretical computations suggesting that the activated monomer-catalyst complex is in an exceedingly high energy state. A lower energy pathway was proposed in which the catalyst (Nuc: in Scheme 2) activates the propagating hydroxyl group through hydrogen bonding.
This insight fostered the design of bifunctional catalysts (Nuc:/E in Scheme 3, wherein Nuc:/E comprises one or more components) capable of simultaneously activating the hydroxyl group in addition to electrophilic activation of the monomer carbonyl.

The synchronized activation of both nucleophile (e.g., hydroxyl group of the initiator) and electrophile (e.g., carbonyl of the cyclic ester) allows a combination of weaker forces to achieve ring opening polymerization. This was demonstrated using various thiourea compounds, which also selectively activated the cyclic ester carbonyl while showing minimal affinity toward analogous linear esters (FIG. 1; Lohmeijer, et al., Macromolecules, 2006, vol 39(5), pp 8574-8583). This selectivity helped to mitigate unwanted transesterification reactions that would otherwise contribute to increased polydispersity (i.e., broadening of the polymer molecular weight range). Moreover, selective carbonyl activation allowed weaker bases, for example (−)-sparteine and N,N-dimethylcyclohexylamine, to be used for hydroxyl activation while still retaining adequate polymerization kinetics. (−)-Sparteine and N,N-dimethylcyclohexylamine are otherwise not active catalysts for the ring opening polymerization of lactide. The polymerization rate can be effectively increased by the use of a more potent hydroxyl activator (such as an amidine or guanidine base), but these stronger bases also predispose the polymerization to transesterification side reactions, and thus higher polydispersities.
The structural diversity of cyclic carbonyl monomers for ring opening polymerizations continues to expand. Accompanying this trend is a growing need for organocatalysts having improved selectivity toward polymer chain growth.